Because PPARα coordinates the fasting response in liver, it can be questioned whether it also contributes to the suppression of glycolysis. Glycolysis serves only as a small generator of ATP whereas it is the principal supplier of pyruvate, which can be further metabolized. Important players in glycolysis are transporters for glucose entry, glucokinase, and the key glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK) (Figure 2). Hepatic glucokinase expression levels and glycolytic flux are mainly regulated in response to the feeding status. Glucokinase transcription is induced by insulin via sterol regulatory element-binding protein 1c (SREBP-1c) and repressed by glucagon [26]. The rate-limiting enzyme PFK is also regulated by insulin [27]. Hepatic expression of PK [28] is tuned independently of insulin, via glucose signaling, which involves binding of carbohydrate response element binding protein to the promoter. The postglycolytic fate of pyruvate is determined by pyruvate dehydrogenase kinase 4 (PDK4), which phosphorylates and inactivates pyruvate dehydrogenase (PDH), the mitochondrial enzyme needed to convert pyruvate to acetyl-coenzyme A (acetyl-CoA) (Figure 2). The latter can enter the tricarboxylic acid (TCA) cycle for energy production
